Therapeutic and diagnostic techniques benefitting from components that heavily absorb light include fluorescent and colorimetric detection1,2, photothermal and photodynamic therapy3-5, photoacoustic tomography (also known as optoacoustic tomography)6-9, optical frequency domain imaging10, and multimodal techniques11, amongst others. Since inorganic nanoparticles interact strongly with light, they can be used as agents for these techniques. For instance, quantum dots are valuable fluorescent probes and have extinction coefficients in the range of 105 to 106 M−1 cm−1,12. Gold nanoparticles are useful for colorimetric detection, photothermal and photoacoustic techniques owing to their much higher extinction coefficients, on the order of 109 to 1011M−1 cm−1,13. Despite recent progress14, optically active inorganic nanoparticles have not yet achieved broad clinical implementation, possibly stemming from drug loading that is generally limited to the nanoparticle surface and concerns regarding long-term safety15-18. In contrast, organic nanoparticles (including liposomes, micelles, nanospheres and polymersomes) have found extensive human therapeutic applications as a result of robust safety profiles, bioavailability and drug delivery capacity18. However, as organic nanoparticles generally do not absorb light in the near infrared, they have been of limited use for biophotonics.
While supramolecular assemblies can be formed by porphyrins, intensely light-absorbing organic small molecules, these constructs have not been thoroughly explored as biological tools owing to a lack of stability, solubility or biophotonic utility19.
Photodynamic therapy combines a photosensitizer with light to eradicate unwanted cells. Compared to other disease treatments, PDT offers the advantage that only where the light and photosensitizer intersect will cells be killed, so that other tissues and organs in the body are spared from damage. In the past decades, PDT has become established as a viable treatment option for a wide range of ophthalmic22, dermatologic23 and in particular oncogenic24 diseases. PDT has emerged as a useful cancer treatment that can destroy unwanted cells through necrosis or apoptosis induced by cellular damage caused by singlet oxygen25. Porphyrin derivatives are the most widely used photosensitizers due to their high singlet oxygen quantum yield and their large extinction coefficients26. However, since conventional porphyrins are hydrophobic molecules, often they must be chemically modified to become more hydrophilic or a delivery vehicle must be used. As such, photosensitizer delivery is an important element of PDT. Liposomal formulations of photosensitizers have found widespread implementation27 and also have shown commercial success (Novartis' Visudyne; Biotec's Foscan, Foslip and Fospeg).
Although PDT has fewer side effects compared to many other treatments, damage to tissue surrounding the target is a limiting factor for more effective treatment. Therefore, PDT that is targeted towards certain unwanted cells is an attractive concept. However, attempts to use antibodies to redirect photosensitizers have been hampered due to the low number of photosensitizers that can be conjugated to an antibody before interfering with antibody function28. Directing photosensitizer-loaded liposomes to targets via antibodies is not practical since photosensitizers redistribute rapidly from liposomes to serum proteins in vivo. Photothermal therapy is a promising disease treatment method in which light is transduced into heat at target sites. The heat produced then destroys the local tissues. Photoacoustic imaging is an emerging imaging technique that relies on nanosecond pulsed lasers and photothermal expansion to generate sound waves that can provide the deepest depth structural resolution of any optical technique.